Preparation of alpha-alkoxy acids and esters



Patented Aug. 30', 1949 PREPARATION OF a-ALKOXY ACIDS AND ESTEBS DonaldJ. Loder, Wilmington, DeL, assignor to E. I. du Pont de Nemours &Company, Wilmington, Del., a corporation of Delaware No Drawing.Application January 14, 1947,

Serial No. 722,077

8 Claims. 1

This invention relates to a process for the preparation of organicesters and more particularly to the preparation of esters of alkoiworganic acids from ethers and alpha-hydroxy aliphatic organic acids ortheir derivatives. This application is a continuation-in-part ofapplication Serial No. 288,585, U. S. Patent 2,302,618.

An object of the present invention is to provide an improved pmcess forthe preparation of alpha-hydroxy aliphatic organic acid esters in whichthe hydrogen of the hydroxyl group has been replaced by an aliphatic,aromatic, cyclic or alicyclic group. Another object of the invention isto provide an economical process for the preparation of alkoxysubstituted acetic acids and their esters from inexpensive rawmaterials. Yet another and more specific object is'to provide a processfor the preparation of alkoxy acetic acid esters, wherein aliphaticethers are interacted with hydroxy acetic acid or its esters; withglycolidm; or with formaldehyde and carbon monoxide. A further object isto provide suitable catalysts for these processes. Other objects andadvantages of the invention will hereinafter appear.

The above objects, and other advantages of the invention which willhereinafter be more fully particularized, are realized by theinteraction of a symmetrical or unsymmetrical ether with (1) analpha-hydroxy aliphatic carboxylic acid or an ester, or (2) an anhydridethereof, preferably in the presence of a suitable catalyst. Thereactions appear to proceed substantially accord with the followingequations:

' (2) ROR-l- (OCHzCO) e- CHz(OR) COOR wherein R designates similar ordissimilar alkyl, aryl, aralkyl, acyl, heterocyclic or alicyclic groups,R1 is a hydrogen or a hydrocarbon radical, and a: is an integer greaterthan 1. In reaction (1) a hydroxy acid will react with an ether to forman alkoxy ester and if an acid is reacted with the ether esters ofalpha-hydroxy carboxylic acids may also be obtained as lay-products ofthe reaction. In reaction (2) esters of alkoxy acetic acids are obtainedfrom ethers and glycolide.

The following equation illustrates the process more specifically withreference to the interaction of dimethyl ether with methyl hydroxyacetate:

(3) CEOCH3+CHz(OH)COOCHs- CH:(OCH:)COOCH:+CH3OH 2 Thus, from dimethylether and methyl hydroxy. acetate, methyl methoxy acetate is obtainedand, in a similar manner, from the diethyl, dipropyl, dibutyl and highersymmetrical ethers; ethyl ethoxy, propyl propoxy, butyl butoxy and thehigher alkoxy acetates, respectively, are produced. In like manner fromthe same ethers and alkyl lactates are obtained methyl m'ethoxy,

ethyl ethoxy, propyl propoxy, butyl butoxy the higher alkoxy lactates.

The above enumerated reactions and similar reactions may, broadlyspeaking, be conducted by The reaction is effected at temperaturesranging from 100 to in the neighborhood of 300 0., the preferred rangefor the interaction of lower ethers, i. e., methyl, ethyl, propyl andbutyl' ethers with carbon monoxide being between 200 and 230 C.Atmospheric pressures may be used,

. although, in order to increase the velocity of the reaction, it isrecommended that pressures in excess of atmospheric be used. Thus,elevated pressures ranging between 5' and 1500 atmospheres or more aresuitablewith a, preferred range between 30 and atmospheres, saidpreferred range of pressures being employed with the preferred catalystconcentrations hereinafter designated. While specific ranges oftemperatures and pressures have been indicated, the reaction may beefi'ected over wide ranges, the optimum conditions varying with theparticular ether and hydroxy acid or derivative reacted and the activityand concentration of the catalyst, if any, employed.

As may be inferred from the above general formulas, a large number ofethers are available for reaction with the hydroxy acids or their derivatives, in accord with the invention. The reac- ROCnHIaORI.

in which n is an integer greater than 1 and R and R1 are either alhl,aryl, or hydrogen, examples of which are monomethyl, ethyl, propyl, andbutyl ethersof ethylene, propylene and diethylene slycols. The etheresters of the glycols are also suitable such, for example, as theacetates and propionates of the monoalkyl ethers of the above designatedglycols. Such ethers as the alkoxy methoxy ethanols can likewise beused.

As previously stated, alpha hydroiqr aliphatic carboxylic acids, theiresters and anhydrides, in general, may be reacted with the ethers. Thehydroxy acetic acid esters which may be reacted include the hydroxyacetic acid esters of methanol, ethanol, nand isopropanol, nandisobutanol, amyl alcohol, and-the higher straight and branched chainalcohols. The glycolides, polyglycolides and other anhydrides of hydroxyacetic acid may also be used, such for example, as diglycolic acid,O-(CHaCOOHTz; diglycolic anhydrlde, (CECO) 2-0; glycolic anhydride,

CH2 (OH) COO.CH:COOH;

glycolide,

GHKLC O polyglycolide, (OCHzCOh, and the like. These glycolides,anhydrides of hydroxy acetic acid or polyglycolides may be considered asesters of hydroxy acetic acid and will be so regarded in thisspecification and the claims appended thereto. Similar esters andanhydrides of the higher alpha-hydroxy aliphatic carboxylic acids maylikewise be used such, for example, as the lactic acid esters, lactidesand other anhydrides, the lactides and anhydrides being consideredherein as esters.

In order to increase the velocity of the reaction it is recommended thata catalyst be employed. In general, the catalyst may be used in amountsranging up to in the order of 1 mole thereof per mole of the ether.Acidic substances, generally, that is, those which give in an aqueousmedium a pH of less than 7 are suitable for catalyzing the reaction.Catalysts which are applicable include, for example, the inorganic acidsand, more particularly, hydrochloric, sulfuric and phosphoric acids ormixtures thereof; inorganic acidic salts such, for example, as potassiumacid sulfate, sodium acid sulfate; the non-metal halides, such as boronfluoride and boron chloride, etc.; organic acids and organic acid saltsmay likewise be employed, such, for example, as oxalic, malonic acidsand their salts.

When boron fluoride is used as the catalyst, it has been found that itmay first be combined with the ether to be reacted and the mixtureperatures and pressures are employed is between approximatel 25 and 75moles of boron fluoride per 100 moles of the ether.

In lieu of reacting the ether with hydroxyacetic acid, its esters orglycolides, the ether may, as stated, be reacted with formaldehyde andcarbon monoxide. As shown in the application of D. J. Loder, Serial No.229,875, filed September 14, 1938, U. S. Patent 2,211,625, hydroxyaceticacid esters are produced in the presence of alcohols, formaldehyde andcarbon monoxide and it has been found that if ethers are employed inlieu of the alcohols, or in conjunction with them, alkoxy substitutedacetic acids are prepared. Under the conditions of such a reaction thedimethyl ether should preferably be present in excess and in the ratioof from 1 to 5 moles of the ether per mole of the formaldehyde, althoughstoichiometrically equimolar proportions are indicated. Under thesecircumstances the more expensive aldehyde is completely reacted whilethe ether may be recovered from the reaction .product and recycledthrough the system.

The reaction product obtained when dimethyl ether is reacted withhydroxy acetic acid, its esters or glycolides, in accord with theinvention, consists essentially of methyl methoxy acetate, together withthe catalyst and unreacted dimethyl ether. The product is separated fromthe catalyst by fractional distillation, preferably under reducedpressures, during which the dimethyl ether and the alkoxy acetate areremoved by distillation and separated from each other by properfractionation. It is usually desirable to carry the separation only topartial completion, allowing a part of the alkoxy acetate product,together I with the catalyst, to remain in the residue which is recycledto the reaction zone for further treatment with added raw materials.

An alternate method of separation, which may be used if boron fluorideis the catalyst, involves the displacement of the alkoxy acetate fromits complex with boron fluoride by the addition of calcium fluoridethereto. The calcium fluoride appears to have a greater afllnity for theboron fluoride than do the alkoxy acetates, and, after the addition ofcalcium fluoride, the alkoxy acetate may be readilycrecovered therefromby distillation under reduced pressure, leaving as a residue .a calciumfluoride-boron fluoride complex from which boron fluoride may berecovered in accord with the process described by R. E. Schultz m U. s.Patent 2,135,458.

(which, for the sake of convenience, will be called a complex) reactedwith the hydroxy acetic acid or glycolide. It is not necessary that allof the ether'to be reacted be combined with the boron fluoride for thereaction proceeds satisfactorily if an ether-boron fluoride complex ispresent in the ratio of from 1 to 10 moles thereof per 100 moles of theether derivative. Complexes of boron fluoride with other compounds such,for example, as complexes of boron fluoride with water (containing, forexample, from 1 to 5 moles of water 'per mole of boron fluoride)methanol, methyl methoxy acetate, glycolide and'the like ma likewise beemployed. When so used from 0.5 mole to 1 mole of the boron fluoride maybe employed per mole of ether, for example. Higher proportions may beused, but generally, those indicated in the designated range cover themore practical ratios. The preferred range for use when the hereinbeforedesignated preferred tom- Examples will now be given to illustratepreferred forms of the invention, although it will be understood thatthe invention is not limited to the details therein given The partsdesignated are by weight unless otherwise indicated and the yields arebased on the hydroxy acetic acid used.

Example 1.A mixture consisting of 68.8 parts of 40% dehydratedhydroxyacetic acid, 207 parts of dimethyl ether and 15.6 parts of boronfluoride dihydrate, BF:(H2O) 2, was charged into a silverlined pressurevessel. The whole was heated at 200 C. with agitation under autogenouspressure for 1 hour. The product was discharged from the cooled reactionvessel and the boron fluoride was neutralized by potassium carbonate.Fractional distillation of the product under 50 mm. of

mercury pressure gave methyl methoxyacetate acaasao heated in asilver-lined pressure vessel with agitation for 2 hours at 225 C.Treatment of the product as described in Example 1 gave methylmethoxyacetate in 40% yield.

Example 3.A silver-lined pressure vessel, lined with silver, was chargedwith 180 parts of methyl hydroxyacetate, 276 parts of dimethyl ether,and 31.2 parts of boron fluoride dihydrate. The mixture was heated withagitation for 2 hours at 225 C. under autogenous pressure. Methylmethoxyacetate, isolated as described above, was produced in 33% yield.

Example 4.A reaction mixture consisting of 45 parts of paraformaldehyde,82 parts of dimethyl ether and 11.4 parts of dimethyl etherboronfluoride complex was processed under 700 atmospheres C0 pressure for 2hours at 200 C. in a copper-lined pressure vessel. The product wastreated with aqueous sodium bicarbonate to neutralize the boron fluoridecatalyst. Methyl methoxyacetate was isolated by extraction with etherand subsequent distillation.

Example 5.-A mixture consisting of 27.5 parts of hydroxyacetic acid, 207partsof dimethyl ether and 15.6 parts of boron fluoride dehydrateBF3(H2O)2, was charged into a silver-lined pressure vessel. The wholewas heated at 200 C. with agitation under autogenous pressure for 1hour. The product was discharged from the cooled reaction vessel and theboron fluoride was neutralized with potassium carbonate. Fractionaldistillation of the product gave methyl methoxy acetate having a boilingpoint of 52 to 55 C. at 42 mm. and a refractive index of 1.3933[25 C.

When referring to dehydrated hydroxyacetic acid in the specification andclaims attached, it will be understood that the word dehydrated" meanscompletely dehydrated.

From a consideration of the above specification it will be appreciatedthat many changes may be made in the details therein given withoutdeparting from the scope of the invention or sacrificing any of theadvantages obtained therein.

I claim:

1. A process for the preparation of compounds selected from the groupconsisting oi alkoxy-substituted acids and esters which compriseseflecting a reaction between an ether and an alphahydroxy aliphaticcarboxylic acid in accord with the equation 6 wherein R designates ahydrocarbon radical, and R1 and x1 designate a radical selected from thegroup consisting of hydrogen and hydrocarbon radicals at a temperatureof to 300 C. and under a pressure between 5 and 1500 atmospheres.

2. The process of claim 1 conducted in the presence of a catalyst whichgives. in an aqueous medium, a pH of less than 7.

3. The process of claim lconducted in the presence of boron fluoride asthe catalyst.

4. A process for the preparation of an alkyl alkoxy acetate whichcomprises interacting an alkyl ether with hydroxyacetic acid in thepresence of an acidic catalyst at a temperature between 100 and 300 C.and under autogenous pressure.

5. A process for the preparation of an alkyl alkoxy acetate whichcomprises interacting in the presence of an acidic catalyst an alkylether with hydroxyacetic acid which has been partially dehydrated at atemperature between 100 and 300 C. and under autogenous pressure.

6. A process for the preparation of methy methoxy acetate whichcomprises heating methyl ether with hydroxyacetic acid in the presenceof sulfuric acid at a temperature between 100 and 300 C. and underautogenous pressure.

7. A process for the preparation of methyl methoxy acetate whichcomprises heating a partially dehydrated hydroxyacetic acid and dimethylether in the presence of hydrated boron fluoride at a temperaturebetween 100 and 300 C. and under autogenous pressure. I

8. A process for the preparation of methyl methoxy acetate whichcomprises heating a reaction mixture having the approximate composition:68.8 parts of 40% dehydrated hydroxyacetic acid, 207 parts of dimethylether, and 15.6

parts of boron fluoride dihydrate at a temperature of approximately 200C. for one hour and under autogenous pressure.

DONALD J. LODER.

REFERENCES CITED The following references are of record in the ills ofthis patent:

UNITED STATES PATENTS Name Date

